Ionizing radiation induces changes in profile of metabolites in serum of cancer patients

Abstract

Radiotherapy causes molecular changes observed at the level of body fluids, which are potential biomarker candidates for assessment of radiation exposure. Here we analyzed radiotherapy-induced changes in a profile of small metabolites detected in sera of head and neck cancer patients using the gas chromatography coupled with mass spectrometry approach. There were about 20 compounds, including carboxylic acids, sugars, amines and amino acids, whose levels significantly differed between pre-treatment and post-treatment samples. Among metabolites upregulated by radiotherapy there was 3-hydroxybutyric acid, whose level increased about three times in post-treatment samples. Moreover, compounds affected by irradiation were associated with several metabolic pathways, including protein biosynthesis and amino acid metabolism.

NMR-based metabolomics in real-time monitoring of treatment induced toxicity and cachexia in head and neck cancer: a method for early detection of high risk patients

“…it has a key role in the regulation of energy homeostasis during food-shortage, it is involved (together with AceAce) in the regulation of insulin signaling, it improves neuronal survival during nutrient deprivation in a mechanism presumably dependent on autophagy as well as regulates inflammation response (Rojas-Morales et al 2016). A complex function of 3HB was also suggested by Ros-Mazurczyk et al (2017). They detected increased 3HB in HNSCC patients using mass spectrometry and suggested that 3HB may be a kind of molecular marker of radiation response.…”

“…The molecular indicators of individual response to radiation would greatly improve monitoring of radiotherapy tolerance and allow early detection of ARS, its prevention and adequate supportive treatment. They could open a possibility for individualized and adaptive treatment programs based on appropriate protective measures.The HNSCC treatment induced toxicity has been extensively studied at both clinical (De Sanctis et al 2016; Schindler et al 2015) and metabolic/proteomic levels (Boguszewicz et al 2016; Guerra et al 2016; Jelonek et al 2017; Roś-Mazurczyk et al 2017; Widlak et al 2016). Since the metabolite composition of blood plasma and serum is known to reflect the response of organisms to disease as well as the treatment-related and environmental factors (Trifonova et al 2013), the patients susceptible to high ARS can be identified using NMR-based metabolomics (Boguszewicz et al 2016) and/or mass spectrometry (Jelonek et al 2017).…”

“…The magnitude of the changes observed in the blood metabolome and proteome were found to correlate with the RT intensity as well as with the volume of side-irradiated normal tissue (Jelonek et al 2017). Another mass spectrometry study by Roś-Mazurczyk et al indicated a significant increase of 3-hydroxybutyrate (D(–)-3-hydroxybutyrate; β-hydroxybutyrate; 3HB) in the post-RT serum of HNSCC patients (Roś-Mazurczyk et al 2017). Unfortunately, they did not correlate their findings with the patients’ clinical state.…”

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

“…Novel metabolites including lipids, glutamate, tryptophan, taurocholate and the Cysteine-Glycine dipeptide were identified 20 . In addition, human serum samples have been analyzed in individuals following radiotherapy 26,27 ; these studies indicated upregulation of biomarkers corresponding to energy metabolism including increased branched chain amino acid synthesis and protein biosynthesis 27 . C57BL/6 mouse biosamples including bone marrow, ileum, muscle, lung, serum, and urine have been analyzed within 12 hours of 6 Gy irradiation and demonstrated differences in DNA methylation pattern, energy expenditure and metabolism of amino acid, glutathione, and bile, respectively 28 .…”

Plasma metabolomic signatures from patients following high-dose total body irradiation

“…Similar marked elevation in the levels of Hyb was observed in the serum of cancer patients treated with radiotherapy. 59 It is noteworthy that high levels of ketone bodies could reduce the rate of b-oxidation of fatty acids. 60 Furthermore, it has been reported that Hyb inhibited lipolysis through the PUMA-G receptor.…”